Anagrelide, is a potent reducer of platelet count induced by a variety of aggregating agents and has the following structure

U.S. Pat. No. 4,146,718 discloses the process for the preparation of ethyl-N-(2,3-dichloro-6-nitrobenzyl)glycine hydrochloride from 1,2,3-trichlorobenzene as depicted in Scheme I via 2,3-dichloro-6-nitrobenzonitrile, which involves the use of poisonous reagents, such as cuprous cyanide. Cyanation is carried out at a temperature of 165° C. which is highly exothermic, uncontrollable and not scalable. 2,3-dichloro-6-nitrobenzonitrile has extreme toxic and skin-irritant properties. Diborane is a flammable gas, used for the reduction of 2,3-dichloro-6-nitrobenzonitrile. The reduction reaction is exothermic, uncontrollable and not feasible industrially.

U.S. Pat. No. 5,801,245 discloses process for the preparation of ethyl-N-(2,3-dichloro-6-nitrobenzyl)glycine hydrochloride from 2,3-dichloro toluene as depicted in Scheme II.

The reaction involves a radical halogenation of the toluene group. The material is purified by column chromatography at each stage which makes the process more tedious and it is not viable industrially. The use of a chromatographic solvent, such as chloroform (which is a known carcinogen), is disadvantageous with respect to industrial application.
US 2003/0060630 discloses a method for making ethyl-N-(2,3-dichloro-6-nitrobenzyl)glycine hydrochloride from 2,3-dichloro benzaldehyde as depicted in Scheme III.

In step (b), the reduction reaction is carried out in high boiling solvents like toluene. The reduction in step (b) and the chlorination in step (c) are sluggish. Also, the chlorination reaction is exothermic and uncontrollable, which leads to formation of more impurities and thereby resulting in low yield (page 4, column 2, and page 5, column 1: 65%). Hence, this prior art process is not viable for industrial scale up.
Because of the difficulties encountered in the processes disclosed in the prior art, there is a need to develop more efficient and economical synthetic route for the preparation of ethyl-N-(2,3-dichloro-6-nitrobenzyl)glycine hydrochloride, which is suitable for industrial scale up. The present invention relates to a new process for the synthesis of Ethyl-N-(2,3-dichloro-6-nitrobenzyl)glycine hydrochloride.
An object of the present invention is to provide a novel process for the synthesis of the intermediate ethyl N-(2,3-dichloro-6-nitrobenzyl)glycine hydrochloride.
Another object of the present invention is to provide novel process for synthesis of anagrelide.
Yet, another object of the present invention is to provide a simple novel process which is useful for application on an industrial scale.